HPV-related papillomatous-condylomatous lesions in female anogenital area Theo Panoskaltsis MD, FRCOG, CCST (UK)
Epidemiology Anal cancer is increasing in both men and women Groups at risk: - HIV (+) men and women - HIV (-) MSM - HIV (-) women at high risk of aquiring HIV - patients with immunosuppression Frisch M et al N Engl J Med 1997
History of receptive anal intercourse Risk factors External genital warts Number of sexual partners, Smoking History of cervical cancer, CIN, Vulvar Ca, VIN
Primary aetiologic factor that cervical and anal cancer share is HPV Anal intercourse is NOT an absolute requirement to aquire anal HPV infection
27% Anal HPV prevalence in HIV(-) women The Hawaii study Hernandez et al, 2005
HPV 16, the most common type
Who should be screened? Men and women HIV (+) MSM Patients with immunosuppression, (organ transplant) Women with lower genital tract HPV disease (VIN, CIN) Men and women with perianal condylomata Edgren G et al Lancet Oncol 2007
Anal Cytology Anal synthetic brush (Dacron swab), inserted to, at least, 4 cm inside canal Glass-fixed slides or Liquid-based Cytology Standard Papanicolaou technique Haematoxylin-Eosin staining
Conventional cytology Specimen contaminated by bacteria
Anal liquid-based cytology LSIL AIN HSIL AIN
Bethesda criteria
Better performed with a colposcope (magnify > 20 times) High-resolution Anoscopy Landmark the transformation Zone (Rectal columnar epithelium meets Anal squamous epithelium)
Anoscopic technique Biopsy of suspicious areas Gauze pad soaked in 3% acetic acid in anal canal, left for 3 min Terminology as in colposcopy (aceticwhite, mosaic, abnormal vessels etc)
Magnifying lenses are inadequate for anoscopy
Plastic disposable anoscopes
Anoscopic technique
Dorsal Position Standard colposcope
Anoscopic technique Biopsy of suspicious areas
Peri-anal and Intra-anal Warts should, always, be biopsied before treatment External AIN 3
Paget s Disease
Normal anal TZ
A/W1 Condyloma
Diffuse A/W1 Condyloma at 7 o clock
AIN 1, staining with lugol s solution
Various degrees of AIN
Keratinised AIN (may harbour HSIL)
Distinct margins AIN 2
HSIL (mosaic-punctation) at 4 o clock
Vascular punctation
Mosaic pattern
Atypical vessels
Neo-vascularisation Suspicion of invasive cancer
AIN 3
Punctation and mosaic AIN 3
Coarse punctation and mosaic early invasive Ca
Superficially invasive Ca
Denuded epithelium invasive Ca
Friable, palpable mass invasive Ca
baby Tischler Forceps
AIN1 Haematoxylin-Eosin Immunohistochemistry (P16 HPV E7 oncogene expression)
AIN 2-3 Haematoxylin-Eosin Immunohistochemistry (P16 HPV E7 oncogene expression)
AIN3 (in-situ) Haematoxylin-Eosin Immunohistochemistry (P16 HPV E7 oncogene expression)
Risk of cancer with AIN3 in healthy individuals Approximately 1:10 Scholefield et al, Br J Surg, 2005
Chemical ablation TCA (trichloroacetic acid) Podophyllin Imiquimod
Electrocautery Physical ablation Infrared coagulation (IRC) - heat from light source directed through a probe - coagulates instead of burning - office procedure Cryotherapy - used for external disease - more than one session Laser therapy
Surgical treatment In suspicion of invasion Anal TZ CANNOT be completely excised Usually combined treatment (excision + ablation) Stenosis and incontinence most serious complications Most recurrences in HIV (+) pts
AIN Treatment 1. Therapeutic Vaccine
AIN Treatment 2. Ablative treatments
AIN Treatment 3. Surgical excision
AIN Treatment 4. Immunostimulants (ALDARA)
ALDARA Complete resolution after 16 weeks
AIN recurrence after treatment
AIN recurrence after Treatment Trichloroacetic Acid 75% Surgical excision 79% Infrared Coagulation 65% 5-FU 50%
Probability of recurrence is related to immunocompetence (HIV) status
Future for HPV-related cancers?
A variety of doctors see HPV patients
Future? Certification for Diagnosis and Treatment of HPV related anal conditions Gynaecologists, Gastroenterologists, Colorectal surgeons could run specialist clinics Collaboration with medical and radiation oncologists Work with an expert pathologist
Is Vaccination the answer to all HPV-related cancers?
Anal Cytology should be followed by Anoscopic biopsy Compared to Histology, Cytology has a 60% sensitivity and specificity for detecting AIN and, specifically, for HSIL (AIN 2,3) sensitivity of only 16%
Anal cancer risk in HIV (+) Pre - HAART 11-19/100,000 Post - HAART 40-78/100,000 VIN3 AIN3
50% long-term recurrence
With 5-FU, reduction in viral load, irrespective of response to tx
USA 2004-2007